Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients

Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients

Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoi...

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Main Authors: Qihong Yan, Ping He, Xiaohan Huang, Kun Luo, Yudi Zhang, Haisu Yi, Qian Wang, Feng Li, Ruitian Hou, Xiaodi Fan, Pingchao Li, Xinglong Liu, Huan Liang, Yijun Deng, Zhaoming Chen, Yunfei Chen, Xiaoneng Mo, Liqiang Feng, Xiaoli Xiong, Song Li, Jian Han, Linbing Qu, Xuefeng Niu, Ling Chen
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Emerging Microbes and Infections
Subjects:
SARS-CoV-2
IGHV3-53
shared clonotype
receptor-binding domain
antibody repertoire sequencing
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2021.1925594
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Summary:Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus-neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients’ antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigen-specific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.
ISSN:2222-1751

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